This proposal describes experiments which are designed to 1) re- evaluate which functional cell types mediate resistance to infection by Listeria monocytogenes, 2) re-examine if humoral antibody production contributes to resistance, and 3) determine at which cellular stages in this response specificity is manifest. The studies will be carried out using the following system, which has been established in this laboratory. Lethally irradiated mice have been reconstituted so that they can resist a challenge infection of live Listeria by injection of normal isologous bone marrow cells and Listeria vaccine, with or without the concomitant injection of thymus cells. Injection of thymus cells alone or thymus cells and macrophages was shown not to be effective. These experiments will be repeated and extended. Resistance will be measured by quantitating the organisms in spleens, livers, and blood of the recipient mice. The research outlined in this proposal will use this system to try to identify which cell population(s) in the bone marrow mediate this resistance, if thymus cells contribute to resistance, and the role macrophages play in this system. In addition, we will re-examine the possible role of humoral antibody formation in resistance to infection, and will re-evaluate the specificity of immunity to infection, particularly with respect to the cell levels at which specificity is important. These studies using Listeria monocytogenes as a prototype intracellular parasite should lead to a clearer understanding of the mechanism of resistance to infection by other intracellular bacteria such as M.tuberculosis.